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Famed novelist Paul Sheldon is the author of a successful series of Victorianromance novels featuring a character named Misery Chastain. Wanting to focus on more serious stories, he writes a manuscript for a new novel that he hopes will launch his post-Misery career. While traveling from Silver Creek, Colorado to his home in New York City, Paul is caught in a blizzard and his car goes off the road, rendering him unconscious. A nurse named Annie Wilkes finds Paul and brings him to her remote home.

Paul regains consciousness and finds himself bedridden with broken legs and a dislocated shoulder. Annie claims to be his "number one fan" and talks a lot about him and his novels. Out of gratitude, Paul lets Annie read his new manuscript. While feeding him, she is angered by the profanity in his new work and spills soup on him, but apologizes. Soon after, Annie reads the latest Misery novel, discovers that Misery dies at the end of the book, and flies into a rage. She reveals to Paul that nobody knows where he is and locks him in his room.

The next morning, Annie forces Paul to burn his new manuscript. When he is well enough to get out of bed, she insists he write a new novel titled Misery's Return, in which he brings the character back to life. Paul complies, believing Annie might kill him. One day, when Annie is away, Paul begins stockpiling his painkillers. He tries poisoning Annie during dinner, but fails. Paul later finds a scrapbook of newspaper clippings about Annie's past. He discovers that she was tried for the deaths of several infants, but the trial collapsed due to lack of evidence. Annie had quoted lines from his Misery novels during her trial. Annie later drugs Paul and straps him to the bed. When he wakes, she tells him that she knows he has been out of his room and breaks his ankles with a sledgehammer to prevent him from escaping again.

The local sheriff, Buster, is investigating Paul's disappearance. When a shopkeeper informs the sheriff he has sold Annie considerable quantities of typing paper, Buster pays Annie a visit. When he finds Paul drugged in the basement, Annie shoots Buster with a shotgun, killing him; she tells Paul that they must die together. He agrees, on the condition that he must finish the novel in order to "give Misery back to the world". He conceals a can of lighter fluid in his pocket.

When the manuscript is done, Paul asks for a single cigarette and a glass of champagne, as is his usual ritual when completing a book, to which Annie complies. Using the match Annie gives him, Paul sets the manuscript on fire, and as Annie rushes to save it, he hits her over the head with the typewriter. They fight and Annie is killed when Paul smashes her in the face with the base of a heavy statue.

Eighteen months later, Paul, now walking with a cane, meets his agent, Marcia, in a restaurant in New York City. The two discuss his first non-Misery novel, and Marcia tells him about the positive early buzz. Paul replies that he does not care, and that he wrote the novel for himself. Marcia asks if he would consider a non-fiction book about his captivity, but Paul declines. Seeing a waitress, he imagines her as Annie. The waitress says she is his "number one fan", to which Paul responds, "That's very sweet of you".

In the original novel, Annie Wilkes severs one of Paul Sheldon's feet with an axe. Goldman loved the scene and argued for it to be included, but Reiner insisted that it be changed so that she only breaks his ankles. Goldman subsequently wrote that this was the correct decision as amputation would have been too severe.[7]

On Rotten Tomatoes, the film received an 89% rating; the consensus reads, "Elevated by standout performances from James Caan and Kathy Bates, this taut and frightening film is one of the best Stephen King adaptations to date."[12]

Roger Ebert liked the film, stating, "It is a good story, a natural, and it grabs us."[13]

In the early 1980s, my wife and I went to London on a combined business/pleasure trip. I fell asleep on the plane and had a dream about a popular writer (it may or may not have been me, but it sure to God wasn't James Caan)...[16]

Misery grossed $10,076,834 on its opening weekend, finishing second at the box office behind Home Alone.[17] It eventually finished with $61 million domestically.[2]

Audiences polled by CinemaScore gave the film an average grade of "A-" on an A+ to F scale.[18]